e-mail: ns@mblcommunications.com


Dr. Sussman is editor of Primary Psychiatry as well as professor of psychiatry and interim chairman in the Department of Psychiatry at the New York University School of Medicine in New York City. Dr. Nelson is Leon J Epstein Professor of Psychiatry and director of Geriatric Psychiatry at the University of California, San Francisco.

Dr. Sussman reports no affiliation with or financial interest in any organization that may pose a conflict of interest. Dr. Nelson is a consultant to Bristol-Myers Squibb, Corcept, Merck, Orexigen, and Sierra Neuropharmaceuticals; is on the advisory boards of Bristol-Myers Squibb, Eli Lilly, and Shire; is on the Data, Safety Monitoring Boards of Medtronics, the National Institute of Mental Health (NIMH), and Orexigen; and receives grant support from the Health Resources and Services Administration and the NIMH.


Both clinicians and researchers have long known that the majority of depressed patients do not achieve or sustain a complete recovery from their disorders on most therapies. This has led to anecdotal reports and to clinical trials that suggest a broad range of interventions involving some combination of medications. The Sequenced Treatment Alternatives to Relieve Depression study1 examined response to treatment in a large sample of 3,671 patients with major depressive disorder. The patients were those typically encountered in primary care and psychiatry settings. The study found that even after 12–14 weeks of adequately dosed citalopram, only 37% of the patients achieved remission. The study indicates that most patients will require additional treatments. The common choices after initial treatment failure are to switch to another antidepressant, add a second antidepressant, start psychotherapy, or augment with a compound not approved for use as an antidepressant. Many different compounds have been used for augmentation including stimulants, modafinil, buspirone, pindolol, estrogen, and testosterone.2,3 Few controlled studies of these agents have been performed, and with the exception of a single modafinil study,4 the controlled studies have failed to show an advantage for augmentation with these agents. Thyroid augmentation has been more extensively studied. Reviews and meta-analyses indicate thyroid augmentation does accelerate response but the placebo-controlled trials in resistant depression fail to show an advantage.5,6

Lithium augmentation also has a long history. The idea for lithium augmentation was suggested by the observation in animal studies that the tricyclic antidepressants (TCAs) increased post-synaptic serotonin receptor sensitivity.4 Because lithium increases serotonin turnover, the thought was that lithium might have rapid effects when added to an ongoing TCA. In fact, the first study of lithium augmentation in depressed human subjects did report improvement within 48 hours in several patients.7 The other observation that supported the idea of a synergistic effect was the induction of mania after the addition of lithium noted in a few case reports.8 This effect would not be expected if lithium were acting independently. In this issue, Lawrence Price, MD, and colleagues provide a comprehensive and critical review of the lithium augmentation literature.

The use of atypical antipsychotics as adjunctive treatments for treatment-resistant depression has a relatively recent history. The use of adjunctive risperidone was first reported in eight patients who had failed selective serotonin reuptake inhibitor treatment in 1999.9 Since 2003, more than a dozen placebo-controlled augmentation trials of atypical antipsychotics in treatment-resistant non-psychotic depression have been reported or presented at meetings. George Papakostas, MD, provides an up-to-date and thoughtful review of this literature, which clinicians will find useful.

A brief case report by Anna Yusim, MD, describes a patient with phantom testicular pain. Like any form of phantom sensation, symptoms involving the genitalia are distressing to patients and difficult for the physician to both explain and treat. As Dr. Yusim notes, <10% of phantom pain patients receive relief with prescribed medication. There is clearly a need for additional research into the psychology and neurobiology of sensory disturbances. This additional information might lead to improved interventions.

Richard H. Weisler, MD, and David W. Goodman, MD, contribute an article on the assessment and diagnosis of adult attention-deficit/hyperactivity disorder (ADHD). They emphasize the need to rule out and factor into treatment decisions the presence of medical conditions and especially to consider cardiovascular risks before initiating treatment of adults with this disorder. Nevertheless, they note that adult ADHD remains under-recognized, underdiagnosed, and undertreated. Improved recognition and treatment should result in improved productivity in school and work as well as lead to better interpersonal relations, especially among family members.

Nadeem Bhanji, MD, and colleagues share the results of a survey of psychiatric physicians about direct-to-consumer (DTC) marketing. They report that surveyed psychiatrists believed that DTC had little significant effect on their prescribing practices, but that over 80% of respondents said they had prescribed medications specifically requested by their patients, often the result of their having seen a DTC advertisement. Among their conclusions is that there is a continued need for clinicians to play an active role about disease states and available treatments. PP


1.     Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients who required one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-1917.
2.    Nelson JC. Augmentation strategies in depression 2000. J Clin Psychiatry. 2000;61(suppl 2):13-19.
3.    Fava M, Rush AJ. Current status of augmentation and combination treatments for major depressive disorder: a literature review and a proposal for a novel approach to improve practice. Psychother Psychosom. 2006;75(3):139-153.
4.    de Montigny C, Aghajanian GK. Tricyclic antidepressants: long-term treatment increases responsivity of rat forebrain neurons to serotonin. Science. 1978; 202(4374):1303-1306.
5.    Altshuler LL, Bauer M, Frye MA, et al. Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry. 2001;158(10):1617-1622.
6.    Aronson R, Offman HJ, Joffe RT, et al. Triiodothyronine augmentation in the treatment of refractory depression. A meta-analysis. Arch Gen Psychiatry. 1996;53(9):842-848.
7.    de Montigny C, Grunberg F, Mayer A, Deschenes JP. Lithium induces rapid relief of depression in tricyclic antidepressant drug non-responders. Br J Psychiatry. 1981;138(3):252-256.
8.    Nelson JC. Use of lithium augmentation in refractory depression. In: Treatment Strategies in Refractory Depression. S. Roose and A. Glassman eds. Washington, DC: American Psychiatric Press, Inc.; 1990;35-49.
9.    Ostroff RB, Nelson JC. Risperidone augmentation of selective serotonin reuptake inhibitors in major depression. J Clin Psychiatry. 1999;60(4):256-259.